E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III non-small cell lung cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Local advanced non-small cell lung cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025052 |
E.1.2 | Term | Lung cancer non-small cell stage III |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Study the effect of metformin when added to definitive locoregional radiotherapy on locoregional control and relapse rate in stage III non-small cell lung cancer (NSCLC) patients receiving sequential chemoradiotherapy |
|
E.2.2 | Secondary objectives of the trial |
Identify subsets of patients who derive maximum benefit of adding metformin to radiotherapy using innovative biomarkers |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the duration of the study. 3. Ability to take oral medication and willing to adhere to the RADFORMIN-regimen. 4. Male or female, ≥ 18 years of age. 5. Histological or cytological proven stage III NSCLC after adequate staging with at least FDG-PET-CT scan, contrast enhanced CT-thorax and contrast-enhanced CT/MRI brain. 6. Absence of diabetes, (diabetes is defined as fasting plasma glucose >126 mg/dL or random plasma glucose >200 mg/dL). 7. Eastern Cooperative Oncology Group (ECOG) performance score (=WHO score) of 0-1. 8. Adequate hematologic, hepatic and renal function as follows: a. Bone Marrow: Absolute neutrophil count ANC ≥ 1,500/mm3 (1.5 x 109/L); White blood cells ≥ 3,000/mm3 (3 x 109/L); Platelets ≥ 100,000/mm3 (100 x 109/L); Haemoglobin ≥ 9 g/dL (5.58 mmol/L). b. Renal function: creatinine clearance of ≥50 mL/min. c. Hepatic function: i. AST and ALT ≤ 2.5 x ULN ii. Bilirubin: ≤1.5 x ULN; for subjects with Gilbert’s syndrome bilirubin > 1.5 x ULN is allowed if no symptoms of compromised liver function are present 9. Adequate pulmonary function in order to be administered definitive radiotherapy. With Forced Expiratory Volume (FEV) > 1.2 litres per second or more than 50% of predicted, and DLCO > 40% predicted. (Values without administration of medical bronchodilation. In case of Tiffeneau < 70% bronchodilation will be administered) 10. Having received at least 2 cycles of platinum-based chemotherapy. This according to institutional standards and without progression (on a restaging CT-scan within 3 weeks after day 1 of the last given cycle, according to RECIST criteria). |
|
E.4 | Principal exclusion criteria |
1. Current use of metformin, insulin or other oral antidiabetic drugs (thiazolidinediones, sulfonylureas, metiglinides, alpha-glucosidase inhibitors, incretin mimitics, dipaptidyl peptidase-4 inhibitors, amylin analogues, SGLT-2-inhibitors) for any reason. 2. Evidence for metastatic disease. 3. Conditions associated with increased risk of metformin-associated lactic acidosis: New York Heart Association class III or IV congestive heart failure, history of acidosis of any type, known kidney injury or disease, alcoholic liver disease or habitual intake of 3 or more alcoholic beverages per day. 4. Known pregnancy or lactating female patients. 5. Known allergic reactions to components of metformin. 6. Prior invasive malignancy within the past year (in remission, without evidence for current active disease and without maintenance therapy). Except non-melanomatous skin cancer, non-invasive carcinoma in-situ of the breast, oral cavity or cervix. 7. Known acquired immune deficiency syndrome. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients free of locoregional progression after 1 year. (LPFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Overall survival (OS) Time-to-progression (TPS) Progression-free survival (PFS) Best response |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |